The Epidemiology and Survival Outcomes of Adult Conjunctival Malignancies in Germany: A Decade-Long Population-Based Analysis (2009-2019).

PURPOSE: This study aims to evaluate the epidemiological patterns, treatment strategies, and survival outcomes of conjunctival malignancies in Germany between 2009 and 2019. METHODS: A total of 1,532 cases were analyzed, with the crude incidence rate calculated. The survival rates were investigated using life tables and Cox regression analysis. RESULTS: The overall incidence rate was 1.7 per million. Incidence rates varied across age groups, peaking in the 75+ age group. Carcinomas (43%), melanomas (30%), and lymphomas (20%), were the most prevalent malignancies. Of the total cases with reported treatment, surgical intervention was undertaken in 64.5% of the patients. The 5-year overall survival rates were 90.4% for lymphomas, 73.8% for melanomas, and 72.9% for carcinomas. Age at diagnosis emerged as a significant prognostic factor in the Cox regression analysis. CONCLUSIONS: This study provides the first population-based incidence data on conjunctival malignancies in Germany, noting a generally low incidence with survival rates comparable to other regions. The findings underscore the importance of consistent reporting and further research into risk factors for a deeper understanding of these malignancies. The study calls for improved reporting systems and further investigations into genetic factors and targeted prevention strategies for high-risk groups.

Declining incidence and improving survival of ocular and orbital lymphomas in the US between 1995 and 2018.

This epidemiological study examined ocular and orbital lymphomas in the United States from 1995 to 2018, using data from the North American Association of Central Cancer Registries database of 87,543 patients with ocular and adnexal malignancies. We identified 17,878 patients (20.4%) with ocular and orbital lymphomas, with an age-standardized incidence rate (ASIR) of 2.6 persons per million (ppm). The incidence was the highest in the orbit (ASIR = 1.24), followed by the conjunctiva (ASIR = 0.57). Non-Hodgkin B-cell lymphoma was the most prevalent subtype (85.4%), particularly marginal-zone lymphoma (45.7%). Racial disparities were noted, with Asia-Pacific Islanders showing the highest incidence (orbit, 1.3 ppm). The incidence increased significantly from 1995 to 2003 (Average Percent Change, APC = 2.1%) but declined thereafter until 2018 (APC = - 0.7%). 5-year relative survival (RS) rates varied, with the highest rate for conjunctival lymphoma (100%) and the lowest for intraocular lymphoma (70.6%). Survival rates have generally improved, with an annual increase in the 5-year RS of 0.45%. This study highlights the changing epidemiological landscape, pointing to initial increases and subsequent decreases in incidence until 2003, with survival improvements likely due to advancements in treatment. These findings underscore the need for further research to investigate the root causes of these shifts and the declining incidence of ocular lymphoma.

The rising tide of rhegmatogenous retinal detachment in Germany: a nationwide analysis of the incidence, from 2005 to 2021.

PURPOSE: This nationwide study aims to delineate the incidence and trends of rhegmatogenous retinal detachment (rRD) in Germany across 17 years (2005-2021). METHODS: We conducted a retrospective cohort study using data from the German Federal Statistics Office and the Institute for the Hospital Remuneration System (InEK). The dataset includes approximately 19 million annual inpatient admissions annually. Retinal detachment was identified through ICD-10 code H33.0. Adjusted incidence rates were estimated after excluding reoperation cases. We used R Statistical Software to calculate estimates to 2021, and Tableau for visualisation. RESULTS: From 2005 to 2021, Germany reported 332,650 rRD cases, with males consistently more affected. Adjusted incidence rose from 15.6 per 100,000 in 2005 to 24.8 in 2021. Variable annual percentage changes in incidence were noted, averaging 4.0% for males and 2.6% for females. The annual mean age of affected individuals ranged from 60.2 to 62 years, with a median age between 62 and 63, suggesting increasing diagnoses at younger ages. Hospital stays declined from 6 to 3.3 days, and higher management rates were observed in Saarland and Rhineland-Palatine. CONCLUSION: The study confirms an increasing incidence of rRD in Germany from 2005 to 2021, particularly among males. These findings call for further research to investigate the underlying causes. Collaboration among healthcare professionals, researchers, and policymakers is essential for effective management and improved visual outcomes.

Smoking-Related Disease Impact in the Eastern Mediterranean Region: A Comprehensive Assessment Using Global Burden of Disease Data.

BACKGROUND: Smoking remains a significant risk factor for numerous health issues, including lung cancer, chronic obstructive pulmonary disease, ischemic heart disease, stroke, and respiratory infections. This study investigates the burden of tobacco-related diseases in the Middle East and North Africa (MENA) region. METHODS: Utilizing the GBD data, we examined the risk of smoking and second-hand smoke exposure and their related causes of death and disability in the 22 MENA countries. Smoking prevalence and disease burden data were analyzed with estimates reported as age-standardized rates. RESULTS: Tobacco abuse accounted for 14.5% of all deaths and 23.2% of deaths tied to known risk factors, with an age-standardized death rate of 110.8 per 100,000. Cardiovascular diseases were the primary cause of smoking-related deaths and DALYs, representing 53.4% of all deaths and 50.3% of all DALYs. This was followed by neoplasms (24.6% of all deaths and 20.3% of all DALYs), chronic respiratory diseases(12.4% of all deaths and 11.9% of all DALYs), and respiratory infections and tuberculosis(4% of all deaths and 3.4% of all DALYs). Second-hand smoking caused 20.5% of tobacco-related deaths and 21.5% of tobacco-related DALYs, disproportionately affecting younger individuals. An increasing disease burden was observed in Lebanon, Turkey, Syria, Tunisia, UAE, and Libya, and declining rates were most evident in Oman and Qatar. CONCLUSION: Our study emphasizes the impact of smoking on cardiovascular disease, the primary cause of smoking-related mortality and morbidity in the MENA region. Our findings highlight the urgent need for effective tobacco control policies and interventions.

The incidence of retinopathy of prematurity in neonates in Germany in 2019; a nationwide epidemiological cohort study.

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness in preterm infants. The incidence of ROP varies widely across countries, with rates as high as 30% in some regions. This study investigated the incidence, risk factors, treatment, and mortality of ROP patients in Germany. Data were extracted from the German Federal Statistical Office (Destatis) diagnosis-related group (DRG) and Institute for the Remuneration System in Hospitals (InEK) databases. Patients with a secondary diagnosis of ROP (ICD-10 code H35.1) in the first 28 days of life were included. Data were extracted for patients admitted between January 1, 2019 and December 31, 2019. The diagnoses and procedures were determined using the German version of the International Classification of Diseases (ICD-10-GM) and the German procedure coding system (OPS). The codes 5-154.xx, 5-155.xx, 8-020.xx, 5-156.9, 6-003.(c&d), 6-007.(2&8) were utilised to denote different ocular treatments. Patient Clinical Complexity Levels were extracted and used to compare ROP with non-ROP patients. A total of 1326 patients with ROP were identified. The incidence of ROP is estimated to be 17.04 per 10,000 live births. The incidence was highest in infants with birth weights less than 500 g and decreased with increasing birth weight. The most common risk factors for ROP were low birth weight, male sex, and prematurity. Of the infants with ROP, 7.2% required ocular treatment. The most common treatment was intraocular injections, followed by photocoagulation. No surgical treatment was required for any of the infants during the study period. The mortality rate for infants with ROP was 60.33 per 10,000. This is higher than the overall neonatal death rate of 24.2 per 10,000. CONCLUSIONS: This study found that the incidence of ROP in Germany is similar to that in other developed countries. The study also found that the mortality rate for infants with ROP is higher than the overall neonatal death rate. These findings highlight the importance of early detection and treatment of ROP in preterm infants. WHAT IS KNOWN: • ROP is a severe eye condition often affecting preterm infants. • Previous data are limited in scope and generalizability. WHAT IS NEW: • Based on a national database, our study found ROP incidence to be 17.04 per 10,000 new births, higher in males (17.71) than in females (16.34). • 7.2% of ROP cases required ocular treatment, inversely correlated with birth weight. • High rates of multimorbidity such as neonatal jaundice (84.69%), respiratory distress syndrome (80.84%), and apnea (78.88%) were observed.

In-Depth Analysis of Incidence and Survival of Lacrimal Gland Malignancies in the United States of America from 1995 to 2018.

PURPOSE: To investigate lacrimal gland malignancies' incidence and survival rates in the USA between 1995 and 2018. METHODS: Incidence and survival data from the North American Association of Central Cancer Registries of lacrimal gland malignancies between 1996 and 2018 were extracted and analyzed. RESULTS: This study analyzed data pertaining to 3620 patients (females 56.7%, n = 2051). A sizable number of patients were 60-79 years of age (45.1%, n = 1633), with a substantial majority being of the non-Hispanic white ethnicity (82.9%, n = 3002). A little above half of patients (52.1%, n = 1886) had presented with a localized disease. Lymphomas represented 59.3% (n = 2146) of lacrimal gland malignancies, while 37% (n = 1339) were carcinomas. The cumulative age-adjusted incidence rate per million was 0.53 for all malignancies, 0.31 for lymphomas, and 0.2 for carcinomas. While the annual crude incidence rate showed a significant steady increase (average annual change of 1.24%; P < .05), age-adjusted rates did not show a similar trend. The five- and 10-year relative survival rates were 88.64 months (95% confidence interval (CI): 85.81-90.93) and 80.26 months (95%CI: 76.21-83.7), respectively. Older age, non-lymphoma tumors, and advanced stage at diagnosis were significantly associated with worse outcomes. Relative survival rates did not show significant changes from 1995 to 2018, irrespective of gender, race or treatment received. CONCLUSIONS: Early detection and localized tumor management can improve survival outcomes for patients with lacrimal gland malignancies. Further research is needed to understand these malignancies' risk profiles and develop more effective treatment strategies.

[Epidemiological impact of the COVID-19 pandemic on enucleation cases in Germany]. / Epidemiologische Auswirkungen der COVID-19-Pandemie auf Enukleationsfälle in Deutschland.

PURPOSE: To determine the rate of enucleation in Germany and the impact that the COVID-19 pandemic may have had on its characteristics. METHODS: The rates of enucleation in Germany during 2019 and 2020 were extracted from the diagnosis-related groups (DRG) registry using the operation and procedure classification system codes 5­163.0 through 5­163.23 and 5­163.x. The data were statistically analyzed. RESULTS: The number of enucleations showed a 16.6% reduction from 1295 cases in 2019 compared to 1080 cases in 2020 (p = 0.17). In both years men averaged 54.1% of cases. Patients older than 65 years represented 53% and 56% of cases in 2019 and 2020, respectively. The most common indication for enucleation in both years was phthisis bulbi (n = 373 and n = 307, respectively), accounting for 29.7% of the cases, followed by choroidal malignancies (24%). Enucleation with the simultaneous introduction of an alloplastic orbital implant into Tenon's capsule represented the most common procedure (38.7% combined 2­year average), followed by a sheathed variant (26.6%) and a bulbar implant made of nonabsorbable microporous material (16.8%), without a significant change between years. Enucleations without the introduction of an implant increased from 7.8% in 2019 to 11.1% in 2020 (p = 0.006). The proportion of patients undergoing a reoperation slightly increased from 5.6% to 8% (p = 0.018). Most procedures (65.6%) were performed in large (> 1000 beds) public hospitals. CONCLUSION: Despite the decrease in the total number of procedures performed, the rate of enucleation in Germany was not significantly altered by the COVID-19 pandemic. The rate of enucleation without implants and reoperations significantly increased.

Survival trends for patients with retinoblastoma between 2000 and 2018: What has changed?

INTRODUCTION: Retinoblastoma (RB) is the most common primary intraocular cancer of childhood. Over the last few decades, a variety of techniques and treatment modalities emerged that improved the survival and ocular salvage rate of patients with RB. We investigated the relative survival trends of patients with RB from 2000 to 2018 by using the Surveillance, Epidemiology, and End Results (SEER) database. DESIGN: Retrospective database review. METHODS: We extracted data from SEER 18 from 2000 to 2018. All patients with clinically diagnosed RB during the study period were included. We utilized SEER*Stat 8.3.9 and JPSurv software to estimate relative 5- and 10-year survival rates and trends and generated descriptive analyses with IBM SPSS. MAIN OUTCOME MEASURES: Patient survival rates at 5- and 10-year after RB diagnosis. RESULTS: RB was diagnosed in 1479 patients within the SEER 18 Program during our study period. The cohort comprised 776 (52.5%) males, 615 (41.6%) non-Hispanic whites, 487(32.9%) Hispanics, 1030 (69.6%) patients with unilateral disease, and 1087 (73.5%) patients with localized disease. Relative survival trends at 5- and 10-year significantly declined over the study periods (-0.42%, and -0.50% annually, respectively) but the decline was not significant in unilateral and bilateral RB cases separately. CONCLUSIONS: Five- and ten-year relative survival trends declined from 2000 to 2018 and were significantly decreasing. Further studies that include more patients are needed to identify the factors contributing to reduced survival of patients with RB over time.

The epidemiology of adults' eyelid malignancies in Germany between 2009 and 2015; An analysis of 42,710 patients' data.

PURPOSE: We report the incidence of malignant tumors of the eyelid in Germany between 2009 and 2015. METHODS: Data pertaining to the period between 2009 and 2015 were extracted from the German Cancer Registry. The International Classification of Diseases for Oncology-3 codes for tumors of the eyelid or canthus were used to identify incidence rates and survival probabilities. Crude and age-standardized incidence rates (ASR) were calculated by age, year, and gender and the individual federated states. Survival was calculated using the Kaplan-Meyer and Life tables methods, and COX-Regression was used to calculate hazard ratios for overall and cancer-specific survival. RESULTS: This study examined data pertaining to 42,710 patients who had been diagnosed with malignant tumors of the eyelid. Basal cell carcinoma was by far the most common tumor of the eyelid (87.1%), followed by squamous cell carcinoma (10.1%) and malignant melanoma (1.1%). ASRs of basal cell carcinoma, squamous cell carcinoma, and melanoma were 65.1, 7.49, and 0.83 per million, respectively. Sebaceous cell carcinoma did not appear to be of high prevalence in Germany. Cancer-specific survival was generally high, exceeding 95%. The overall survival of patients with melanoma was considerably lower than those with other cancers. Both survival rates were inferior to that of basal cell carcinoma (74.9%). Cancer-Specific survival at five years for all groups exceeded 95%. CONCLUSIONS: The incidence rates of malignant lid tumors match that of the European countries but shows a different pattern than Asian countries.

FoxP3 expression by retinal pigment epithelial cells: transcription factor with potential relevance for the pathology of age-related macular degeneration.

BACKGROUND: Forkhead-Box-Protein P3 (FoxP3) is a transcription factor and marker of regulatory T cells, converting naive T cells into Tregs that can downregulate the effector function of other T cells. We previously detected the expression of FoxP3 in retinal pigment epithelial (RPE) cells, forming the outer blood-retina barrier of the immune privileged eye. METHODS: We investigated the expression, subcellular localization, and phosphorylation of FoxP3 in RPE cells in vivo and in vitro after treatment with various stressors including age, retinal laser burn, autoimmune inflammation, exposure to cigarette smoke, in addition of IL-1ß and mechanical cell monolayer destruction. Eye tissue from humans, mouse models of retinal degeneration and rats, and ARPE-19, a human RPE cell line for in vitro experiments, underwent immunohistochemical, immunofluorescence staining, and PCR or immunoblot analysis to determine the intracellular localization and phosphorylation of FoxP3. Cytokine expression of stressed cultured RPE cells was investigated by multiplex bead analysis. Depletion of the FoxP3 gene was performed with CRISPR/Cas9 editing. RESULTS: RPE in vivo displayed increased nuclear FoxP3-expression with increases in age and inflammation, long-term exposure of mice to cigarette smoke, or after laser burn injury. The human RPE cell line ARPE-19 constitutively expressed nuclear FoxP3 under non-confluent culture conditions, representing a regulatory phenotype under chronic stress. Confluently grown cells expressed cytosolic FoxP3 that was translocated to the nucleus after treatment with IL-1ß to imitate activated macrophages or after mechanical destruction of the monolayer. Moreover, with depletion of FoxP3, but not of a control gene, by CRISPR/Cas9 gene editing decreased stress resistance of RPE cells. CONCLUSION: Our data suggest that FoxP3 is upregulated by age and under cellular stress and might be important for RPE function.

Uveal melanoma and marital status: a relationship that affects survival.

BACKGROUND: Marital status influences the presentation and outcome of various cancers. We explored the relationship between marital status and survival of uveal melanoma (UM) and factors influencing this relationship. METHODS: We conducted a retrospective cohort study on patients diagnosed with UM and registered in the Surveillance Epidemiology and End Results program between 1973 and 2017. Cox regression model was conducted to calculate the hazard ratio of overall and cancer-specific survival rate and delineate the effect of each confounder. RESULTS: The study involved 10,557 patients with a male-to-female ratio of 1:1.1. Most of the diagnosed patients were aged between 40 and 79 years (81%). Married patients (62%) represented the majority, followed by singles (12%), widowed (11%), and then divorced patients (7%). Single patients were the youngest group (mean age of 59.3 years) while widowed patients were the oldest (mean age of 75.8 years). In the Cox regression model for overall survival, married and single patients exhibited the best overall survival (no significant difference in between them), both surpassing divorced and widowed patients. Married patients were at a significantly lower risk to die from UM than divorced patients. Female patients and younger age groups showed the best overall and cancer-specific survival. CONCLUSION: Maintained marriages improved the survival of UM patients. Widowed and divorced patients should be included in specially designed support programs during their cancer management.

The epidemiology of uveal melanoma in Germany: a nationwide report of incidence and survival between 2009 and 2015.

PURPOSE: To calculate the overall incidence of uveal melanoma in Germany and to compare incidences in different German states. In addition, we computed the overall and cancer-specific survival rates nationwide. METHODS: Incidence data for the period between 2009 and 2015, covering the entire German population, was collected through the German Center for Cancer Registry. ICD-O-3 topography codes C69.3-C69.4 and histology codes for melanoma subtypes were used to collect the incidence data. Confidence Intervals with a level of 95% (95% CI) were calculated for rates. Survival was calculated using the Kaplan-Meier. The log-rank test was used for survival comparisons. RESULTS: This study comprised 3654 patients with uveal melanomas, including 467 (12.8%) with iridial and ciliary body tumors. The overall age-standardized incidence rate (ASIR) was 6.41 person per million. Generally, the ASIR was higher in males than females (6.67 (95% CI 6.37-6.98) vs. 6.16 (95% CI 5.88-6.45 per million). Higher crude incidence rates were noted in the northeastern states (12.5 per million (95% CI 10.5-14.7) in Mecklenburg-Vorpommern) compared with the southwestern states (2.1 per million (95% CI 1.7-2.6) in Hessen). The 5-year overall survival stood at 47%, while the cancer-specific survival stood at 84%. Multivariate analysis showed that women, younger patients, and patients living in Berlin achieved significantly higher overall survival. CONCLUSION: Overall ASIR of uveal melanoma in Germany indicates that the disease is more common in males and that it follows the same geographical distribution previously noted in central European countries, with the highest incidence in northern parts of Germany.

Pediatric ependymoma: A single-center experience from a developing country.

BACKGROUND: Ependymomas are the third most common pediatric central nervous system (CNS) tumors, accounting for 6-12% of brain tumors in children. Management of these tumors remains challenging and recurrence occurs in over 50% of cases, mainly when complete resection is not achieved before radiotherapy. The 5-year overall survival (OS) ranges from 39 to 64%, with a 5-year progression-free survival (PFS) rate of 23-45%. The study aimed to describe the OS and PFS rates of cases of pediatric ependymoma. It also aimed to evaluate the effects of different variables on disease outcomes. Variables examined included patient age, the extent of surgical resection, radiotherapy and chemotherapy delivered, the histopathological subtype of the tumor, primary tumor location, and extent of the disease at presentation. Last, the challenges that potentially compromise treatment outcomes in resource-limited countries were to be highlighted. METHODS: This is a retrospective cohort study, representing a single-center experience that included 47 pediatric patients treated at the National Cancer Institute, Cairo University, between January 2009 and December 2014. RESULTS: Median follow-up stood at 23.5 months (range: 2-77 months). The average 3-year OS and PFS rates were 43.7 and 43.3%, respectively. CONCLUSION: The extent of surgical excision (maximal resection) and the adequacy of postoperative radiotherapy were the only two factors that had significantly affected the outcome. Understandably, treatment outcomes for ependymomas in developing countries still lag behind best reported outcomes, mainly due to inadequate surgical excision and postoperative radiotherapy.

Second primary malignancies of eye and ocular adnexa after a first primary elsewhere in the body.

PURPOSE: The eye and its adnexal structures can give rise to first or consecutive primary malignancies or to encounter metastasis. Our aim was to define the characteristics of the second primary neoplasms affecting the eye and its adnexa and find the risk modifying factors for them after malignancies elsewhere in the body. METHODS: We have queried the Surveillance, Epidemiology and End-Results "SEER"-9 program of the National Cancer Institute for the malignancies of the eye and its adnexa that occurred between 1973 and 2015. The malignancies were ordered chronologically according to their incidence: first or second primary malignancies. The tumors were classified according to ICD-O-3 classification. Standardized incidence ratios (SIR) and survival probabilities were calculated for subgroups. RESULTS: Among 3,578,950 cancer patients, 1203 experienced a second malignancies of the eye and its adnexa. The first malignancy was diagnosed between 50 and 69 years of age in 58.94% of them. The eyelid showed 280 events, while 50 in lacrimal gland, 181 in the orbit, 21 in the overlapping lesions, 15 in optic nerve, 148 in the conjunctiva, 9 in the cornea, 6 in the Retina, 379 in the choroid, and 93 in the ciliary body. The SIR of a second malignancy after a prior non-Hodgkin lymphoma was 2.42, and in case of previous skin carcinomas it was 3.02, melanoma of skin, and 2.13 and 1.58 in oral cavity/pharynx malignancies. The second ocular and adnexal neoplasms increased steadily over the 5-year periods on contrary to first primary neoplasms. The survival of patients affected with first ocular and adnexal neoplasms was significantly higher than those with second ocular and adnexal neoplasms. On the other side, second primary ocular and adnexal tumors showed a better survival than second primary malignancies elsewhere. CONCLUSIONS: The epidemiological differences between first and second ocular and adnexal primaries suggest different underlying mechanisms. Careful ocular examination should be integrated in the long-term follow-up plan of cancer patients. Special attention should be given to patients with non-Hodgkin's lymphoma and melanoma as first primary.

Unilateral retinoblastoma; natural history and an age-based protocol in 248 patients.

OBJECTIVES: We aimed to study the clinical state and prognosis of patients with unilateral retinoblastoma who were being treated at a paediatric comprehensive cancer centre in a limited-resource country, to assess the different phases of treatment and the success of different, more complex real-life models. SUBJECTS: In this retrospective study, we created a snapshot of our retinoblastoma database for the period between 2007 and 2015. Patients whose data were included in the study were followed up until 2016. Out of a total of 744 screened patients, we included data of 248 patients who had been diagnosed with unilateral retinoblastoma. RESULTS: As classified as per the International Retinoblastoma Classification, 1 patient presented with group A, 21 with group B, 39 with group C, 104 with group D and 83 with group E retinoblastoma. Chemotherapy was the initial line of treatment in 115 patients and enucleation in 133 others. Later, 141 patients (56.9%) required further management. Patients had a mean ocular survival time of 20.8 months. Nine patients developed extraocular disease at a later stage of management: five after upfront enucleation and four after neoadjuvant chemotherapy. Mean overall survival time stood at 90.2 months. Four and three deaths were recorded in groups D and E, respectively. A single patient died in the initial chemotherapy arm, while six passed away in the initial enucleation arm. CONCLUSION: Our study highlights the importance of initial chemotherapy and close follow-up after enucleation of classes D and E affected eyes even in absence of germline mutations.

Uveal melanoma-associated cancers revisited.

BACKGROUND: Uveal melanoma (UM) is the most common primary ocular malignancy of adults. A small group of patients was found to express familial predisposition. Moreover, it may be preceded or followed by other malignancies elsewhere in the body. We aim to compare the incidence of UM and other associated cancers and study the factors that may influence each condition. PATIENTS AND METHODS: We have collected the data from the Surveillance, Epidemiology and End Results database of nine US cancer registries for UM patients between 1973 and 2015. We calculated the standardised incidence ratios for single primary UM, first primary and second primary UM, and compared the groups for multiple factors. RESULTS: A total of 4946 patients were included in the study; 3863 with single primary UM, 646 developed a second primary malignancy following UM, and 437 patients developed second primary UM following a previous primary malignancy. The risk of developing UM increased after leukaemia, melanoma of the skin and prostate. On the other side, the risk of developing melanoma of the skin, thyroid, renal and other eye and orbit malignancies has increased significantly after initial UM. This risk was more evident in the age group between 50 and 70 years old. Cancer-specific survival was significantly higher in UM associated with other malignancies group compared with single primary UM. CONCLUSION: Our study showed a different behaviour of the UM when associated with other tumours that exceed the known spectrum of hereditary UM. Further studies are required to dissect the genetic background of this behaviour.

The outcome of childhood adrenocortical carcinoma in Egypt: A model from developing countries.

Adrenocortical carcinoma (ACC) is a rare, aggressive endocrine neoplasm. Complete surgical resection is the single most important treatment. Most available information has been learned from experience with its more frequent adult counterpart. In this study, we assessed the features and survival outcome of patients with ACC at Children's Cancer Hospital Egypt (CCHE). Patients diagnosed at CCHE between July 2007 and November 2016 were followed up on until November 2018. Patients with stages I and II were operated upon, while stages III and IV had received combinations of doxorubicin, etoposide, platinol, and mitotane (DEPM) beside the attempt to conduct surgery when feasible. Data belonging to 18 patients (7 men and 11 women) were analyzed; median age at diagnosis was 48.5 months. Sixteen patients had presented with secreting tumors. Six patients were diagnosed with stage I disease; four with stage II; three with stage III; and five with stage IV carcinoma. By the end of this study, 10 patients have survived; five-year overall survival of 66.3%. Surviving patients were all of stage I or II diseases and were all in remission. Seven patients who did not survive died due to tumor progression, while one patient died after chemotherapy. The prognosis of ACC is essentially dependent on a successful complete resection of the tumor and thus on the initial tumor stage. The mitotane and DEP protocols may help control tumor growth in the advanced stages for only short periods. Key pointsInitial stage and resectability are the main indicators of outcomes in adrenocortical carcinoma.Chemotherapeutic agents used in developed countries did not achieve the same outcomes.Further molecular-pharmacology differentiation is needed for various ethnic populations.

Inhibition of Ca2+ channel surface expression by mutant bestrophin-1 in RPE cells.

The BEST1 gene product bestrophin-1, a Ca2+ -dependent anion channel, interacts with CaV 1.3 Ca2+ channels in the retinal pigment epithelium (RPE). BEST1 mutations lead to Best vitelliform macular dystrophy. A common functional defect of these mutations is reduced trafficking of bestrophin-1 into the plasma membrane. We hypothesized that this defect affects the interaction partner CaV 1.3 channel affecting Ca2+ signaling and altered RPE function. Thus, we investigated the protein interaction between CaV 1.3 channels and bestrophin-1 by immunoprecipitation, CaV 1.3 activity in the presence of mutant bestrophin-1 and intracellular trafficking of the interaction partners in confluent RPE monolayers. We selected four BEST1 mutations, each representing one mutational hotspot of the disease: T6P, F80L, R218C, and F305S. Heterologously expressed L-type channels and mutant bestrophin-1 showed reduced interaction, reduced CaV 1.3 channel activity, and changes in surface expression. Transfection of polarized RPE (porcine primary cells, iPSC-RPE) that endogenously express CaV 1.3 and wild-type bestrophin-1, with mutant bestrophin-1 confirmed reduction of CaV 1.3 surface expression. For the four selected BEST1 mutations, presence of mutant bestrophin-1 led to reduced CaV 1.3 activity by modulating pore-function or decreasing surface expression. Reduced CaV 1.3 activity might open new ways to understand symptoms of Best vitelliform macular dystrophy such as reduced electro-oculogram, lipofuscin accumulation, and vision impairment.